1. Field of the Invention
Compositions and methods for cosmetic genetic modification of cells that have cosmetic function are provided. Compositions and methods are also provided for determining, using various animal models, whether expression and/or levels of skin proteins and other biomolecules such as collagen, elastin, extracellular matrix proteins, proteoglycans, growth factors has a cosmetic rejuvenation effect on the skin, and for evaluating the cosmetic genetic modification of substantially intact cells having a cosmetic function.
2. Description of the Related Art
Expression and/or levels of skin proteins and other biomolecules such as collagen, elastin, extracellular matrix proteins, proteoglycans, growth factors, endogenous antioxidant enzymes, and/or DNA repair enzymes, may decline substantially with age, to produce undesirable changes in cosmetic appearance. For example, fibroblast and kertinocyte responsiveness to growth factor stimulation may decline with age. In contrast, certain proteins may increase to produce undesirable changes in skin and other cells having cosmetic function. For example, matrix metalloproteinase-1 (MMP-1) protein may increase in skin cells; as MMP-1 accelerates collagen breakdown, the build-up of MMP-1 can be detrimental to the skin.
Age-related changes may include sagging, thinning, or wrinkling of the skin. There are topical compositions that are formulated to improve the appearance of skin, but generally, such formulations require frequent and multiple applications (i.e., once or twice daily year round). Alternatively, invasive intervention (e.g., plastic surgery, laser resurfacing, and injection procedures) may help to reduce sagging and wrinkling of the skin. Still, many individuals are reluctant to undergo a surgical procedure for a non-therapeutic (i.e., cosmetic) reason. Thus, there is a need for cosmetic compositions and methods that offer a more permanent solution than many skin creams can offer, but that do not require plastic surgery or other types of invasive intervention.
Genetic therapy can provide a targeted approach for the improvement, treatment and maintenance of cells having cosmetic function. For example, certain genes appear to be involved in skin tissue maintenance and repair. Numerous growth factors, including epidermal growth factor (EGF), transforming growth factor (e.g., TGF-beta), fibroblast growth factor (FGF), insulin-like growth factor (IGF-1), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), and PDGF may be involved in wound healing (see e.g., Grazul-Bilska et al., Drugs of Today, 2003, 39:787-800; S. Werner and R. Grose; Physiol. Rev., 83:835-870, 2003). For example, a mixture of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-1), granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin (IL-8, IL-6), tumor necrosis factor (TNF-alpha), transforming growth factor (TGB-beta) and matrix proteins may be used to improve wound healing (reviewed in Jimenez and Jimenez, Am. J. Surgery, 2004, 187:56S-64S). Also, insulin-like growth factor (IGF-1) may be used to increase muscle hypertrophy (Barton-Davis et al., Acta Physiol. Scand., 1999, 167:301-305). Thus, improving the production and function of specific proteins by molecular targeting of the genome of cells involved in cosmetic function may provide a means to improve the longevity and health of such cells.